Rheumatoid Arthritis: Europe

Davies K, Woo P, Anonymous00129. · Department of Rheumatology, Great Ormond Street Hospital, London WC1N 3EJ, UK. · Rheumatology (Oxford). · Pubmed #12154212 links to  free full text

Abstract: OBJECTIVES: To establish opinion and clinical practice of senior clinicians working with children with rheumatic diseases with regard to immunization and to determine whether or not this is in accordance with current recommendations. To review published guidelines on the subject and examine the evidence base supporting them. METHODS: A questionnaire was sent to all consultant members of the British Paediatric Rheumatology Group. Information on a variety of issues relating to immunization practice in children with rheumatic diseases was collected. A review of published guidelines and the medical literature on the subject was undertaken to assess current recommendations for immunization in patients on immunosuppressive agents and the evidence supporting these. RESULTS: A number of different sources of information are being used to decide whether or not to immunize patients with rheumatic diseases. Clinical practice varies between individuals. Areas of discordance include the doses of corticosteroids and disease-modifying drugs at which significant immunosuppression is felt likely to occur, the level of immunosuppression conferred by rheumatological diseases themselves and whether or not vaccination should be deferred in the presence of active disease. There was also variation in policy with regard to immunizations not part of the routine recommended schedule. CONCLUSIONS: There is variation in both opinion and clinical practice regarding immunization in children with rheumatic diseases amongst senior clinicians working in the field of paediatric rheumatology. This reflects the lack of consistency between various sets of published guidelines and their non-specificity for rheumatic diseases and their treatment, and the lack of published evidence on the safety and efficacy of different vaccines in these situations. Further research is indicated in the hope that more specific guidelines may be developed for this not uncommonly encountered area of uncertainty.

Hull RG, Anonymous00033. · Queen Alexandra Hospital, Cosham, Portsmouth, Hampshire PO6 3LY, UK. · Rheumatology (Oxford). · Pubmed #11709617 links to  free full text

This publication has no abstract.

Kalden JR, Scott DL, Smolen JS, Schattenkirchner M, Rozman B, Williams BD, Kvien TK, Jones P, Williams RB, Oed C, Rosenburg R, Anonymous00047. · Department of Internal Medicine III, University of Erlangen-Nuremberg, Germany. · J Rheumatol. · Pubmed #11550964 No free full text.

Abstract: OBJECTIVE: We previously reported that the new disease modifying antirheumatic drug leflunomide resulted in significant improvement in functional ability compared with placebo and sulfasalazine in a 6 month double blind, randomized, Phase III trial in rheumatoid arthritis (RA). The current study compared functional disability in cohorts of patients with RA from the initial study who volunteered to continue treatment with leflunomide or sulfasalazine. METHODS: The Health Assessment Questionnaire (HAQ) was used to assess functional ability in patients completing 6 months of therapy who chose to continue in double blinded 12 and 24 month extensions. Patients on active regimens continued taking leflunomide 20 mg/day or sulfasalazine 2 g/day; those taking placebo were switched at Month 6 to sulfasalazine. RESULTS: Leflunomide significantly improved patients' functional ability compared to placebo (p < or = 0.0001) and sulfasalazine (p < or = 0.01) at 6 months. These changes were seen as early as Month 1, and continued improvements were seen in 12 and 24 month cohorts. Mean HAQ scores were significantly improved with leflunomide compared with sulfasalazine at 24 months (-0.65 vs -0.36; p = 0.0149); corresponding changes in HAQ Disability Index (DI) were -0.73 vs -0.56 and were not statistically different. Leflunomide is safe and well tolerated and no unexpected adverse events were noted during the 2 year period; diarrhea, nausea, and alopecia were less frequent with continued treatment. CONCLUSION: These longterm data confirm leflunomide improves functional ability as shown by reductions in HAQ scores. The benefit of leflunomide is reflected in other efficacy criteria, such as global assessments and the American College of Rheumatology response rates, all of which showed significantly more improvement with leflunomide than sulfasalazine at 24 months.

Keitel W, Genth E, Gromnica-Ihle E, Häntzschel H, Kalden JR, Mathies H, Raspe HH, Schneider M, Warnatz H, Zacher J, Abholz HH. · Rheumaklinik und Rheumaforschungsinstitut, Aachen. · Z Rheumatol. · Pubmed #10929443 No free full text.

Abstract: The guideline "Joint Swelling" is addressed to primary care physicians--general practitioners, internists or orthopedists without special experience in rheumatology. It provides a framework for interviewing patients, as well as for physical, laboratory and imaging examinations and for selection of treatment appropriate to the level of primary care. Situations which call for urgent evaluation and criteria for referral to rheumatologists are described. The appendix contains comments on signs and symptoms to differentiate arthralgia from joint swelling and on the diagnostic value of a history of joint swelling without confirmation by the physician. Further recommendations for the evaluation of patient history and physical and technical examinations are given in a tabular form. The significance of laboratory and imaging procedures is discussed.

Wautier JL, Schmid-Schönbein GW, Nash GB. · Institut National de la Transfusion Sanguine, Paris, France. · Clin Hemorheol Microcirc. · Pubmed #10517484 No free full text.

Abstract: The measurement of leukocyte rheology in vascular disease is a recent development with a wide range of new opportunities. The International Society of Clinical Hemorheology has asked an expert panel to propose guidelines for the investigation of leukocyte rheology in clinical situations. This article first discusses the mechanical, adhesive and related functional properties of leukocytes (especially neutrophils) which influence their circulation, and establishes the rationale for clinically-related measurements of parameters which describe them. It is concluded that quantitation of leukocyte adhesion molecules, and of their endothelial receptors may assist understanding of leukocyte behaviour in vascular disease, along with measurements of flow resistance of leukocytes, free radical production, degranulation and gene expression. For instance, vascular cell adhesion molecule (VCAM-1) is abnormally present on endothelial cells in atherosclerosis, diabetes mellitus and inflammatory conditions. Soluble forms of intercellular adhesion molecule (ICAM-1) or VCAM can be found elevated in the blood of patients with rheumatoid arthritis or infections disease. In the second part of the article, possible technical approaches are presented and possible avenues for leukocyte rheological investigations are discussed.

Wulffraat NM, Kuis W, Petty R. · Department of Paediatric Immunology and Rheumatology, University Hospital for Children 'Het Wilhelmina Kinderziekenhuis', Utrecht, The Netherlands. · Rheumatology (Oxford). · Pubmed #10501434 links to  free full text

This publication has no abstract.

Schmidt K, Rüther W. · Klinik für Orthopädie und Rheumaorthopädie, Katholisches Krankenhaus Dortmund-West, Zollernstrasse 40, 44379, Dortmund. · Z Rheumatol. · Pubmed #18779969 No free full text.

This publication has no abstract.

Smolen JS, Aletaha D. · Division of Rheumatology, Medical University of Vienna, Vienna, Austria. · Nat Clin Pract Rheumatol. · Pubmed #18461061 No free full text.

This publication has no abstract.

Boers M. · Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands. · Nat Clin Pract Rheumatol. · Pubmed #18446137 No free full text.

This publication has no abstract.

Schiavon F, Favero M, Carraro V, Riato L. · U.O.C. di Reumatologia, Azienda Ospedale-Università, 35128 Padova, Italia. · Reumatismo. · Pubmed #18432319 links to  free full text

Abstract: Septic arthritis (SA) is a clinical emergency with considerable morbidity and mortality that can lead to rapid joint destruction and irreversible loss of function. The reported incidence varies from 2-5 cases per 100.000 individuals per year in the general populations to 70 cases per 100.000 individuals annually among patients with rheumatoid arthritis (RA). Predisposing factors are immunosuppressive and corticosteroids therapy and RA "itself". The expected decrease in incidence of SA was not seen over the last 20 years period but we can, on the contrary, expect an increase in the frequency of its appearance because of the population ageing, the increasingly prosthetic joint replacement, the ability of the bacteria to evade clearance by the host immune response and the rapidly growing number of patients with RA, ankylosing spondylitis and psoriatic arthritis treated with tumour necrosis factor alpha (TNF alpha) antagonists. Up to now there have been conflicting reports regarding joint infections in patients under anti-TNF therapy but according to data from Deutsch as well as the British register there might be an increase in the incidence of joint infections in anti-TNF treated patients. Microscopic analysis and culture of synovial fluid are fundamental diagnostic tools in the evaluation of possible joint sepsis. Sonographic guidance of arthrocentesis led to successful aspiration of difficult-to-access joints as shoulder and hip. There is controversy over which mode of drainage of septic synovial fluid should be employed but needle aspiration appear to be preferable to surgical treatment as an initial mode of treatment of SA. Rheumatologists should have a central role in the diagnosis and management of SA.

van den Berg WB. · Rheumatology Research & Advanced Therapeutics, Radboud University, Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlandsw. · Nat Clin Pract Rheumatol. · Pubmed #18073726 No free full text.

This publication has no abstract.

Rüther W. · Orthopädische Klinik der Rheumaklinik Bad Bramstedt, Universitätsklinikum Hamburg-Eppendorf. · Z Rheumatol. · Pubmed #17896423 No free full text.

This publication has no abstract.

Märker-Hermann E. · Klinik Innere Medizin IV, Dr. Horst Schmidt Kliniken (HSK) GmbH, HSK Wilhelm Fresenius Klinik, Aukammallee 39, 65191, Wiesbaden, Deutschland. · Z Rheumatol. · Pubmed #17006701 No free full text.

This publication has no abstract.

Roudier J. · INSERM UMR 639, Université de la Méditerranée,13005, Marseille, France. · Arthritis Res Ther. · Pubmed #16542468 links to  free full text

Abstract: The factors that trigger the development of extraarticular features of rheumatoid arthritis (RA) are still unknown. HLA-DR alleles such as HLA-DR4 and HLA-DR1 are associated with the risk to develop RA. A large scale study from Sweden and the Mayo Clinic suggests that HLA-DR4, but not HLA-DR1, is associated with the risk to develop extraarticular RA.

Cutolo M. · Department of Internal Medicine, University of Genova, Genova, Italy. · Clin Exp Rheumatol. · Pubmed #15083879 No free full text.

This publication has no abstract.

Martignoni ME, Kunze P, Friess H. · Department of General Surgery, University of Heidelberg, Im Neuenheimer Feld 110 Germany. · Mol Cancer. · Pubmed #14613583 links to  free full text

Abstract: In recent years many efforts of researchers and clinicians were made to improve our knowledge of cachexia syndrome. Not only cancer, but also many chronic or end-stage diseases such as AIDS, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, tuberculosis and Crohn's disease are associated with cachexia, a condition of abnormally low weight, weakness, and general bodily decline which deteriorates quality of life and reduces the prognosis of the patients who suffer from it. In the present editorial we will focus cachexia related on cancer and provide some insight into this prognosis-limiting syndrome.

Loetscher P, Moser B. · Theodor-Kocher Institute, University of Bern, Switzerland. · Arthritis Res. · Pubmed #12106492 links to  free full text

Abstract: In about 20% of patients with rheumatoid arthritis, B and T lymphocytes recruited into the inflamed synovium are organized into complex microstructures, which resemble secondary lymphoid organs. The development of such lymphoid aggregates with germinal centers appears to contribute to the pathogenesis of the disease. Growing evidence indicates that chemokines and their receptors control the recruitment and positioning of leukocytes as well as their organization into node-like lymphoid structures. Here, we comment on recent studies highlighting the importance of chemokines in rheumatoid arthritis, in particular of B-cell-activating chemokine-1 in lymphoid neogenesis in the inflamed synovium.

Jonsson R, Haga HJ, Gordon TP. · · Scand J Rheumatol. · Pubmed #11132201 No free full text.

Abstract: Sjögren's syndrome is a chronic autoimmune and rheumatic disorder. Most patients have mild to moderate complaints and this may explain the great discrepancy in prevalence found in population studies compared to studies performed in the clinic. However, there is no straightforward and simple diagnostic test for Sjögren's syndrome, although several classification criteria have been designed. Initiatives have been taken to propose a new set of classification criteria in a joint effort by research groups in Europe and USA. A large number of autoantibodies have been reported in Sjögren's syndrome where, in some cases, the antibodies are correlated with the extent and severity of disease. The finding of serum autoantibodies directed against the muscarinic M3 receptor is an important advance in understanding the pathogenesis of not only the impaired glandular function but also associated features of autonomic dysfunction in some patients. The treatment of primary Sjögren's syndrome is still mainly symptomatic.

Sergejeva S, Lindén A. · Department of Clinical Medicine of Technomedicum, Tallinn University of Technology, Tallinn, Estonia. · Endocr Metab Immune Disord Drug Targets. · Pubmed #19519466 No free full text.

Abstract: Discovered in 1993, IL-17 has been the focus of intensive research during the last decade, in particular because of its neutrophil-accumulating capacity in several mammalian organs. We now know that the IL-17 family includes as a minimum 6 members, of whom at least IL-17A and IL-17F can be produced by T cells. Thus, IL-17 is positioned at the interface of acquired and innate immunity and constitutes a link between T cell activity and the accumulation of neutrophils locally in organs. Interestingly, there is now accumulating evidence that IL-17 has effects on myeloid cells other than neutrophils as well, namely on cells of the monocyte lineage. This review article scrutinizes the evidence that IL-17 exerts a functional impact on the cytokine production and functional activity in cells of the monocyte lineage in health and disease. Notably, this evidence includes data suggesting that there are conditions in which cells of the monocyte lineage are likely to play a significant pathogenic role and where IL-17 is directly controlling the activity of these key effector cells.

Hönscheid A, Rink L, Haase H. · Institute of Immunology, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany. · Endocr Metab Immune Disord Drug Targets. · Pubmed #19519463 No free full text.

Abstract: The trace element zinc is a crucial cofactor for many proteins involved in cellular processes like differentiation, proliferation and apoptosis. Zinc homeostasis is tightly regulated and disturbance of this homeostasis due to genetic defects, zinc deficiency, or supplementation influences the development and the progression of various infectious and autoimmune diseases. The immune system is strongly impaired during zinc deficiency, predominantly the cell-mediated response by T-lymphocytes. During zinc deprivation T-lymphocyte development, polarization into effector cells, and function are impaired. This leads to reduced T-cell numbers, a decreased ratio of type 1 to type 2 T-helper cells with reduced production of T-helper type 1 cytokines like interferon-gamma, and compromised T-cell mediated immune defense. Accordingly, disturbed zinc homeostasis increases the risk for infections, and zinc supplementation restores normal immune function. Furthermore, several disorders, like mycobacterial infections, asthma, diabetes, and rheumatoid arthritis are accompanied by decreased zinc levels and in some cases disease progression can be affected by zinc supplementation. On the molecular level, apoptosis of T-cell precursors is influenced by zinc via the Bcl-2/Bax ratio, and zinc ions inhibit caspases-3, -6, -7, and -8. In mature T-cells, zinc interacts with kinases involved in T-cell activation, like protein kinase C and the lymphocyte protein tyrosine kinase (Lck), while higher zinc concentrations are inhibitory, reducing the activities of the interleukin-1 receptor-associated kinase (IRAK) and calcineurin. Taken together, zinc homeostasis influences T-lymphocytes via several molecular targets, leading to a modulation of T-cell-dependent immune responses.

Guillevin L. · Service de Médecine Interne, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris René Descartes, Paris, France. · Rheumatology (Oxford). · Pubmed #19487226 No free full text.

Abstract: Vasculitis can occur either as a primary condition or secondary to CTDs, infection, medication or malignancy. This article reviews the clinical presentation and management of vascular disease associated with SLE and SS, as well as the primary necrotizing vasculitides. Although pulmonary arterial hypertension (PAH) has traditionally been considered a rare complication of SLE, estimates of its prevalence range from 0.5% to 14% and it has a significant impact on prognosis. In contrast to PAH associated with other CTDs, patients with SLE respond well to immunosuppressive agents (cyclophosphamide in conjunction with corticosteroids). Improvements or stabilization of PAH symptoms and quality of life have also been observed with the oral, dual endothelin receptor antagonist, bosentan. SS is associated with a range of cutaneous and systemic signs of vasculitis. Immunosuppressive agents are effective, but are associated with an increased risk of lymphoma. The necrotizing vasculitides include WG, Churg-Strauss syndrome and microscopic polyangiitis, and are characterized by autoantibodies to neutrophil cytoplasmic constituents. WG is one of the most common forms of vasculitis; patients usually present with signs of respiratory disease. All three necrotizing vasculitides respond to cyclophosphamide and corticosteroids, while the less toxic AZA and MTX are effective for maintenance therapy. Future therapeutic approaches may include rituximab, plasma exchanges, the TNF antagonist infliximab and haematopoietic stem cell transplantation.

Barnes PJ, Adcock IM. · National Heart and Lung Institute, Imperial College, London, UK. · Lancet. · Pubmed #19482216 No free full text.

Abstract: Glucocorticoid resistance or insensitivity is a major barrier to the treatment of several common inflammatory diseases-including chronic obstructive pulmonary disease and acute respiratory distress syndrome; it is also an issue for some patients with asthma, rheumatoid arthritis, and inflammatory bowel disease. Several molecular mechanisms of glucocorticoid resistance have now been identified, including activation of mitogen-activated protein (MAP) kinase pathways by certain cytokines, excessive activation of the transcription factor activator protein 1, reduced histone deacetylase-2 (HDAC2) expression, raised macrophage migration inhibitory factor, and increased P-glycoprotein-mediated drug efflux. Patients with glucocorticoid resistance can be treated with alternative broad-spectrum anti-inflammatory treatments, such as calcineurin inhibitors and other immunomodulators, or novel anti-inflammatory treatments, such as inhibitors of phosphodiesterase 4 or nuclear factor kappaB, although these drugs are all likely to have major side-effects. An alternative treatment strategy is to reverse glucocorticoid resistance by blocking its underlying mechanisms. Some examples of this approach are inhibition of p38 MAP kinase, use of vitamin D to restore interleukin-10 response, activation of HDAC2 expression by use of theophylline, antioxidants, or phosphoinositide-3-kinase-delta inhibitors, and inhibition of macrophage migration inhibitory factor and P-glycoprotein.

Neves C, Jorge R, Barcelos A. · Interna Complementar de Medicina Interna, Unidade de Reumatologia e Serviço de Medicina 2, Hospital Infante D. Pedro EPE - Aveiro. · Acta Reumatol Port. · Pubmed #19449473 No free full text.

Abstract: INTRODUCTION: Methotrexate is a folic acid antagonist recognised as one of the most important DMARD's in the rheumatoid arthritis treatment. Although the indisputable efficacy and the good tolerance profile, the broad toxicity spectrum is very variable with respect both to symptoms and intensity. The side effects vary from malaise and asthenia to pneumonitis or pancytopenia, which can be fatal. OBJECTIVES: To review the adverse effects of methotrexate in the treatment of rheumatoid arthritis. MATERIALS AND METHODS: Literature review, using Medline as a starting point, searching with the keywords "methotrexate", "toxic effects", "adverse effects", "rheumatoid arthritis". The relevant papers and selected references found therein were used. RESULTS: The gastrointestinal symptoms are the most frequent, but myelossupression and pneumonitis are the most feared ones. Elevation of transaminases could indicate hepatic toxicity, placing the risk of cirrhosis. Cutaneous lesions, neurologic symptoms, changes in the bone metabolism, teratogenecity and hyperhomocysteinemia are other examples of the adverse effects of methotrexate. The post-dosing reactions are still not well known. The folate supplementation is important in the prevention of folate metabolism dependent symptoms. The farmacogenomics may help to identify patients in greater risk for multiple side effects. CONCLUSIONS: Knowing and monitoring the methotrexate side effects is extremely important and should be carefully considered in order to prevent both therapeutic withdrawals due to toxicity as well as fatal outcomes.

Lomax AR, Calder PC. · Institute of Human Nutrition, School of Medicine, University of Southampton, Tremona Road, Southampton SO16 6YD, UK. · Curr Pharm Des. · Pubmed #19442167 No free full text.

Abstract: A number of studies have been performed examining the influence of various probiotic organisms, either alone or in combination, on immune parameters, infectious outcomes, and inflammatory conditions in humans. Some components of the immune response, including phagocytosis, natural killer cell activity and mucosal immunoglobulin A production (especially in children), can be improved by some probiotic bacteria. Other components, including lymphocyte proliferation, the production of cytokines and of antibodies other than immunoglobulin A appear less sensitive to probiotics. Probiotics, including lactobacilli and bifidobacteria, administered to children can reduce incidence and duration of diarrhoea, but the precise effects depend upon the nature of the condition. Probiotic supplementation can reduce the risk of travellers' diarrhoea in adults, but does not affect duration. The effect of probiotics on other infectious outcomes is less clear. Probiotics may benefit children and adults with irritable bowel syndrome and adults with ulcerative colitis; studies in Crohn's Disease are less clear. Probiotics have little effect in rheumatoid arthritis. Probiotic supplementation, especially with lactobacilli and bifidobacteria, can reduce risk and severity of allergic disease, particular atopic dermatitis; early supplementation appears to be effective. Overall, the picture that emerges from studies of probiotics on immune, infectious and inflammatory outcomes in humans is mixed and there appear to be large species and strain differences in effects seen. Other reasons for differences in effects seen will include dose of probiotic organism used, duration of supplementation, characteristics of the subjects studied, sample size, and technical differences in how the measurements were made.

Volpi N, Schiller J, Stern R, Soltés L. · Department of Biologia Animale, University of Modena & Reggio Emilia, Via Campi 213/d, I-41100 Modena, Italy. · Curr Med Chem. · Pubmed #19442142 No free full text.

Abstract: Hyaluronan (hyaluronic acid, HA) is a linear naturally occurring polysaccharide formed from repeating disaccharide units of N-acetyl-D-glucosamine and D-glucuronate. Despite its relatively simple structure, HA is an extraordinarily versatile glycosaminoglycan currently receiving attention across a wide front of research areas. It has a very high molar mass, usually in the order of millions of Daltons, and possesses interesting visco-elastic properties based on its polymeric and polyelectrolyte characteristics. HA is omnipresent in the human body and in other vertebrates, occurring in almost all biological fluids and tissues, although the highest amounts of HA are found in the extracellular matrix of soft connective tissues. HA is involved in several key processes, including cell signaling, wound repair and regeneration, morphogenesis, matrix organization and pathobiology. Clinically, it is used as a diagnostic marker for many disease states including cancer, rheumatoid arthritis, liver pathologies, and as an early marker for impending rejection following organ transplantation. It is also used for supplementation of impaired synovial fluid in arthritic patients, following cataract surgery, as a filler in cosmetic and soft tissue surgery, as a device in several surgical procedures, particularly as an anti-adhesive following abdominal procedures, and also in tissue engineering. This review will provide an overview of the structure and physiological role of HA, as well as of its biomedical and industrial applications. Recent advances in biotechnological approaches for the preparation of HA-based materials, and as a component of tissue scaffolding for artificial organs will also be presented.